Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center, 111 Michigan Avenue NW, Washington, DC 20010-2970, USA.
J Neurooncol. 2011 Jun;103(2):197-206. doi: 10.1007/s11060-010-0378-3. Epub 2010 Sep 2.
Although known for the important function in the immune system, MHC class I molecules are increasingly ascribed an alternative role in modifying signal transduction. In medulloblastoma, HLA class I molecules are associated with poor prognosis, and can induce ERK1/2 activation upon engagement with ligands that bind to incompletely assembled complexes (so called open conformers). We here demonstrate that ERK1/2 activation in medulloblastoma can occur in the absence of endogenously synthesized β2m, formally excluding involvement of closed HLA class conformation. In addition, several experimental observations suggest that heterogeneity of HLA class I expression may be a reflection of the status of original cells before transformation, rather than a consequence of immune-based selection of HLA-loss mutants. These results contribute to our understanding of an immune system-independent role of HLA class I in the pathology of medulloblastoma, and cancer in general.
虽然 MHC Ⅰ类分子在免疫系统中具有重要功能，但它们在信号转导修饰中的作用也日益受到关注。在髓母细胞瘤中，HLA Ⅰ类分子与不良预后相关，并在与不完全组装复合物（所谓的开放构象）结合的配体结合后，可诱导 ERK1/2 激活。我们在此证明，在没有内源性合成的β2m 的情况下，髓母细胞瘤中的 ERK1/2 激活也可以发生，从而正式排除了封闭 HLA Ⅰ类构象的参与。此外，一些实验观察结果表明，HLA Ⅰ类表达的异质性可能反映了原始细胞在转化前的状态，而不是 HLA 缺失突变体基于免疫选择的结果。这些结果有助于我们理解 HLA Ⅰ类在髓母细胞瘤以及一般癌症发病机制中的一种与免疫系统无关的作用。
